DESCRIPTION: (Applicant's Description) Cigarette smoking, which is considered as a model environmental exposure, has been the major cause of lung cancer in United States. Dietary consumption of fruits and vegetables which are rich in antioxidants, such as vitamin C, has shown protective effects against smoking-related cancer risk in several epidemiological studies. We hypothesize that daily oral vitamin C supplementation decreases carcinogen- or free radical-induced DNA damage in lymphocytes (surrogate tissue) of current smokers. To test this hypothesis, we propose to analyze two biomarkers, i.e., smoking-related PAH-DNA adducts and oxidative DNA damage (8-OHdG) by 32-P-postlabeling assay in lymphocyte DNA of current smokers. This project will use blood samples from a previously completed vitamin C intervention trial involving 200 current smokers. In the original project, subjects received oral supplementation of vitamin C in doses of 1 or 4 grams per day or placebo for 4 months. Serum ascorbic acid level was measured by HPLC prior to randomization and one month after treatment on vitamin C. Effects of vitamin C supplementation on the individual susceptibility to genotoxic agents was evaluated by quantification of bleomycin-induced chromosomes breaks in short-term peripheral lymphocyte cultures. The current proposal intends to evaluate the efficacy of oral vitamin C supplementation on DNA damage in the same study subjects. Fifty samples each from the high dose group (4 g per day) and the placebo group will be evaluated at 2 time points. Correlations between serum vitamin C level, mutagen sensitivity and DNA-damaged induced by smoking will be evaluated. Results of this study are expected to demonstrate the feasibility of DNA adducts as reliable biomarkers in the risk assessment for smoking-related cancer and to show that vitamin C offers protection by scavenging free radicals, thus decreasing the oxidative DNA damage.